Nasir Shumyila, Vohra Muhammad Sufyan, Gul Danish, Swaiba Umm E, Aleem Maira, Mehmood Khalid, Andleeb Saadia
Department of Industrial Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.
Department of Pharmacy, Abbottabad University of Science and Technology, Havelian, Pakistan.
Int J Microbiol. 2020 Oct 29;2020:8831322. doi: 10.1155/2020/8831322. eCollection 2020.
The emergence of multidrug-resistant pathogens such as methicillin-resistant (MRSA), the chief etiological agent for a range of refractory infections, has rendered all -lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line -lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.
耐多药病原体如耐甲氧西林金黄色葡萄球菌（MRSA）的出现，它是一系列难治性感染的主要病原体，使得所有β-内酰胺类药物对其无效。随着对糖肽类药物（治疗MRSA的一线抗生素）耐药性的出现，治疗过程进一步复杂化。联合使用现有抗菌药物进行抗生素联合治疗可能提供一种即时治疗选择。测定了18种不同市售抗生素的最低抑菌浓度（MIC）以及它们90种可能的两两组合和64种三联组合，以筛选出5种最佳组合。然后分析这些组合的时间杀菌动力学，以找出协同杀菌组合，随后在其他随机选择的MRSA分离株上进行测试。在包括左氧氟沙星-头孢他啶；阿莫西林/克拉维酸-妥布霉素；阿莫西林/克拉维酸-头孢拉定；阿莫西林/克拉维酸-氧氟沙星；以及哌拉西林/他唑巴坦-妥布霉素在内的前5种组合中，发现有3种组合具有协同作用。左氧氟沙星-头孢他啶在80%的测试临床MRSA分离株中表现出协同作用。较低代的一线β-内酰胺类药物联合使用时可有效对抗MRSA感染。除糖肽类药物外的其他抗生素联合使用可能仍然有效。
